RU2452470C1 - Liposome suspension composition for prevention and treatment of respiratory infections, particularly tuberculosis (versions) and method of aerogene delivery thereof - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology. A liposome suspension composition for prevention and treatment of respiratory infections, particularly tuberculosis, contains liposomes, propylene glycol pine wood extract, propylene glycol sage extract, marigold, bee balm and eucalyptus essences, Carbopol, glycerin, blanose, epo-phen, kathon, sodium hydroxide and water. In other version, the liposome suspension composition for prevention and treatment of respiratory infections, particularly tuberculosis, contains liposomes as a basis, propylene glycol pine wood extract, propylene glycol dandelion, burdock and cornflower extracts, lavender, bergamot and schizandra essences, Carbopol, glycerin, blanose, epo-phen, kathon, sodium hydroxide and water. A method for prevention and treatment of respiratory infections, particularly tuberculosis by inhalations; it involves aerosol processing of a room by the presented liposome suspension composition by making 10 applications of a dosing cock with the area of 20 sq. m.

EFFECT: using the offered invention enables widening the spectrum of ecologically safe high-effective immune-enhancing agents with antimicrobial, anti-viral and fungicidal effect for massive prevention and treatment of respiratory infections, including tuberculosis.

3 cl, 2 ex, 2 tbl, 2 dwg

Description

The invention relates to biotechnology and can be used in biology, pharmacology, medicine, cosmetics and veterinary medicine.

Liposomes (LPs) or phospholipid vesicles are used to create systems for the targeted transport of biologically active substances in order to increase the therapeutic activity of finished products. The effectiveness of drugs due to the property of their tropism to the membranes of living cells, on the principle of "similar to similar." This ensures the rapid penetration of drugs into tissues and delivery of components incorporated into them to their destination. LPs are almost instantly sorbed on the surface of living cells and interact with them. Thus, lipophilic and hydrophilic active substances of various molecular weights can be delivered to the cells using liposomes. These properties of drugs are already widely used in medicine, cosmetology and light industry. In addition, phospholipid membranes of liposomes are able to carry out cell repair at the molecular level. Lecithin is an antioxidant and is part of the membranes of all living cells. Violation of the balance of phospholipids leads to a change in the viscosity of the membranes, and therefore to various pathological changes, therefore, maintaining the balance of phospholipids protects cells from impaired functional abilities. The use of liposomes eliminates the phospholipid syndrome, increases cell survival in extreme conditions, and allows you to quickly restore the epidermal skin barrier.

The transport of substances by liposomes ensures their almost complete utilization and the possibility of reducing the working concentration, which has an economic effect and is advisable when working with therapeutic substances that have side effects.

Known therapeutic and prophylactic agent with liposomes containing Dorogov antiseptic stimulant (RF patent No. 2126676 A61K 7/00 7/48, 35/12, 1999, BI No. 6), its successful use in dermatology and cosmetology since 1998.

Known therapeutic and prophylactic agent containing silver embedded in the liposome membrane with antiseptic effect for the prevention and treatment of acne (RF patent No. 2167650. Bull. 15 2001).

Known pharmaceutical composition with liposomes for the prevention and treatment of bone resorption of various etiologies, the method of its transdermal delivery and treatment method (patent No. 2225165, A61K 31/663. Bull. No. 15, 2008).

It is known to use drugs and prophylactic agents based on extracts from pine, eucalyptus, sage, aspen and other plants in the treatment of the respiratory system, including tuberculosis (RF patent 2210379 "Anti-tuberculosis drug" (aspen bark extract).

This tool is based on aspen bark of a bitter taste and is poorly tolerated by patients.

Known cosmetic means of reparative action "Gel balm repair" gel "Loriol" for irrigation of the throat and others (RF patent No. 2173140 A61K 9/5097/127, 2001, Bull. No. 25).

Known means cannot be used for air decontamination and aerogenous delivery of active substances.

In the treatment of respiratory diseases, there is always a lipid component (internal fat, an extract from eggs) and medicinal plants (T.A. Vinogradova, B.I. Gazhev, V. M. Vinogradov, V. K. Martynov, Practical herbal medicine in the recipes of traditional medicine Publishing House Moscow - St. Petersburg, 2001).

A disadvantage of the known means is that the antibacterial and immunomodulating effect is local, and it is impossible to carry out large-scale preventive and therapeutic measures, as well as their narrow spectrum of action.

The closest in technical essence to the present invention is a composition with fungicidal, antimicrobial and virucidal action from a suspension of liposomes with phytoextracts (options), containing as active agents three fractions from the monarda plant in combination with other phytopreparations in liposomal form (RF patent No. 2372096, IPC A61K 36/78, 9/06, A61K 36/15, 2008. Bull. No. 26).

The disadvantage of the prototype is its limited activity for the prevention and treatment of airborne infections, in particular tuberculosis, as well as the low effectiveness of the drug due to the absence of flavonoids, carotenoids, tar, coumarins, which reduces the bactericidal, immunomodulating and antioxidant properties of the composition.

The objective of the invention is the creation of new agents with antimicrobial, antiviral and fungicidal activity and at the same time having a pronounced immuno-strengthening effect, based on liposomes with extracts from pine, sage, and essential oils of marigold, monarda, eucalyptus, bergamot, lavender for the prevention and treatment of airborne -drip infections, including tuberculosis.

As a result of the use of the present invention, the range of environmentally friendly highly effective immuno-fortifying agents with antimicrobial, antiviral and fungicidal effects is expanding for large-scale prevention and treatment of airborne infections, including tuberculosis by their aerogenous administration, as well as for air decontamination. The use of the proposed tool provides the treatment and prevention of airborne infections and tuberculosis, the most simple and physiological method: strengthening the human body immunity and suppressing the growth of pathogenic and conditionally pathogenic microorganisms.

The above result is achieved by the fact that the proposed composition of suspended liposomes for the prevention and treatment of airborne infections, in particular tuberculosis, characterized in that it contains liposomes, propylene glycol extract from pine wood, propylene glycol extract of sage, marigold essential oils, monarda and eucalyptus, carbopol, glycerin, blanose, epofen, caton, sodium hydroxide and water in the following ratio, wt.%:

lipofolk 0.1-5.0 pine wood propylene glycol extract 0.1-1.2 propylene glycol sage extract 1.0-2.0 marigold essential oil 0.3-0.9 monarda essential oil 0.1-0.7 eucalyptus essential oil 0.01-0.1 carbopol 0.1-0.5 glycerol 0.5-3.0 blanose 0.01-0.1 epofen 0.001-0.1 caton 0.01-0.1 sodium hydroxide 0.3-0.7 water rest

In another embodiment, a composition of suspended liposomes for the prevention and treatment of airborne infections, in particular tuberculosis, characterized in that it contains liposome propylene-glycolic extract from pine wood, propylene-glycolic extracts of dandelion, burdock and cornflower, essential oils of lavender, bergamot and Schisandra chinensis, carbopol, glycerin, blanose, epophene, caton, sodium hydroxide and water in the following ratio, wt.%:

lipofolk 0.2-5.0 pine wood propylene glycol extract 0.05-1.0 propylene glycol dandelion extract 0.5-1.0 propylene glycol burdock extract 0.3-0.7 propylene glycol dandelion extract 0.7-1.4 lavender essential oil 0.1-0.5 bergamot essential oil 0.1-0.7 Chinese Schisandra essential oil 0.05-0.2 carbopol 0.1-0.5 glycerol 0.5-3.0 blanose 0.01-0.1 epofen 0.001-0.1 caton 0.01-0.1 sodium hydroxide 0.2-0.6 water rest

The technical result is also achieved by the fact that in the proposed method for the prevention and treatment of airborne infections, in particular tuberculosis, aerosolized aerosol treatment of the premises of the proposed composition from a suspension of liposomes is carried out by 10 presses on the dispensing trigger with an area of 20 square meters.

The proposed method for saturating the air with necessary substances is simple and applicable in any situation and situation. Aerogenous administration in this case allows you to simultaneously affect a large number of people or animals, and targeted delivery by liposomes when they are inhaled provides a reduction in the dose of the active substance.

Spraying can be carried out locally directly above the head for inhalation 3-4 times a day for 2-5 clicks on the trigger dispenser.

The technique of active transport through liposomes allows the use of extracts from pine wood and sage, essential oils of marigold, monarda and eucalyptus in one stable composition and achieve a preventive and therapeutic effect in a short period of time.

The aerogenic method of administering the composition involves the suspension of liposomes directly into the alveoli of the lungs, mucous membranes of the nasopharynx and trachea, and the targeted action of active substances on the cells of the immune system and epithelium of the respiratory system, as well as penetration into the bloodstream. In addition, spraying the agent in airspace ensures the binding of lipid vesicles to the surface of microorganisms and the direct effect of bactericidal components, as a result of which the level of microbiological air pollution is significantly reduced.

When spraying the proposed composition through the nozzle of a mechanical dispenser, the smallest drops of gel containing water, liposomes with phytoextracts and sorbents bind a suspension of bacteria and dust particles and release volatile volatile molecules of phytoncides into the air. In a drop, when it is deposited on the surface, a certain concentration of phytoncides is created and the cells of pathogenic bacteria are inactivated, which ensures a quick, within 15 minutes, reduction of microbial air contamination, and the maximum effect is observed after 6 hours and lasts for 24 hours or more, in depending on the intensity of air flow.

Freshening and increasing air humidity is achieved after 30-60 seconds.

The method of application consists in spraying the agent using a mechanical dispenser-dispenser on 150, 500, 750 ml bottles around the perimeter of the room at an angle of 45-60 degrees, based on 1 ml of the product per 2 sq.m To clean the air, treatment should be carried out 1-3 times a day, it is possible in the presence of people in view of the safety of the product.

To obtain an immuno-strengthening effect, air treatment must be carried out daily, two to three times. An increase in the efficiency of medical staff is noted, the well-being of patients improves according to subjective data. Changes in blood counts are gradual, noted after application of the drug for 30 days or more. The composition used by the method of aerosolization allows you to recreate the methods of balneology in any room of the urban environment to restore the body's forces in a natural biological way (for example, simulating a stay in a pine forest).

Given the problem of the development of antibiotic resistance by many microorganisms, and the absence of such a phenomenon when using plant extracts, the method can be used to prevent many diseases transmitted by airborne droplets.

Thus, using the proposed composition for the aerogenous administration of essential oils and extracts included in liposomes, it is possible to prevent infections and strengthen the immune system by purifying and enriching the air, making up for the deficiency of essential plant elements. To do this, you can use any type of atomizer, i.e. the method is reproducible in rooms of various sizes in accordance with the instructions for use and consumption rates.

The process of preparing the proposed composition from a suspension of liposomes with phytoextracts.

Preparation of active ingredients.

Carbopol is prepared by its swelling method in deionized water.

Blanose is prepared by the method of its swelling in water with constant stirring and heating to 60 ° C.

Glycerin is mixed with a caton and introduced into the mixing tank.

Water-soluble components are dissolved immediately before administration.

To form liposomes, prepare the fat phase: lipofolk (a complex of vitamins and phospholipids from egg yolks) is mixed with essential oils and extracts.

2. Technology of preparation.

Gelling agents, a lipid phase are introduced into the mixing tank, homogenized on an ultra-fast homogenizer, then sorbents are introduced, the gel is polymerized with sodium hydroxide, mixed well until a homogeneous mass, pH is checked (from 6.9 to 7.6).

Example 1. A composition of a suspension of liposomes for an arogenous method for the prevention and treatment of airborne infection using the example of tugetone “Tageton” (preparation No. 2).

This composition contains liposomes, propylene glycol extract from pine wood, propylene glycol extract of sage, essential oils of marigold, monarda and eucalyptus, carbopol, glycerin, blanose, epofen, cato, sodium hydroxide and water in the following ratio, wt.%:

lipofolk 0.3 pine wood propylene glycol extract 0.9 propylene glycol sage extract 1,0 marigold essential oil 0.7 monarda essential oil 0.3 eucalyptus essential oil 0.05 carbopol 0.3 glycerol 2.0 blanose 0.01 epofen 0.005 caton 0,07 sodium hydroxide 0.6 water rest

The composition contains a suspension of small liposomes ranging in size from 100 to 500 nm, stabilized in a system of polymers acting as stimulators of immunocompetent cells and inhibitors of microbial cells, can be used for the treatment and prevention of respiratory diseases.

Marigold essential oil contains a large amount of Ocimene, Pinene, Camphene, which increases the bactericidal effect of the composition, and carotenoids and polyphenols provide a deodorizing and antioxidant effect.

The pine extract is obtained by gentle ultrasonic extraction of wood sawdust.

The study of the bactericidal effect of pine extraction resin on the growth of bacteria Mycobacterium tuberculosis (Rv37) is presented in table. one.

Table 1 The resin content of pine g / ml % suppression 0.001 fourteen** 16* 0.002 39 36 0.003 89 84 0.004 93 94 0.005 92 98 0.01 Turbidity due to sample SE Note: * with OD / 600 - 0.37 * and 0.76 **

Example 2. A composition of a suspension of liposomes for an aerogenic method for the prevention and treatment of airborne infections using the Sensitive tuberculosis as an example (preparation No. 1).

The composition contains liposomes, propylene-glycolic extract from pine wood, propylene-glycolic extracts of dandelion, burdock and cornflower, essential oils of lavender, Chinese bergamot and schisandra, carbopol, glycerin, blanose, epofen, caton, sodium hydroxide and water in the following ratio of components, wt.%:

lipofolk 1,2 pine wood propylene glycol extract 0.5 propylene glycol dandelion extract 1,0 propylene glycol burdock extract 0.3 propylene glycol dandelion extract 0.7 lavender essential oil 0.2 bergamot essential oil 0.1 Chinese Schisandra essential oil 0.1 carbopol 0.2 glycerol 1,0 blanose 0.01 epofen 0.05 caton 0,07 sodium hydroxide 0.5 water rest

The method of aerogenic delivery of the proposed composition from a suspension of liposomes allows for large-scale prevention and treatment of airborne infections, in particular tuberculosis.

Studies have been conducted to study the effectiveness of the proposed composition from a suspension of liposomes with phytoextracts for the treatment of acute tuberculosis of mice according to the guidelines for the study of the anti-tuberculosis activity of pharmacological substances.

In the treatment of airborne infections, liposomes or liposomes with plant extracts and sorbents are inhaled into the alveoli, deposited on the surface of the airway epithelium and, by activating the phagocytic function of macrophages, carry out instant repair of epithelial cells. In addition, a certain concentration of phytoncides is created and mycobacteria are inactivated. The results on the anti-tuberculosis activity of the drugs were obtained on the basis of the Federal State Research Center for Applied Microbiology and Biotechnology of the Federal Service for Supervision of Consumer Rights Protection and Human Well-being of the Russian Federation. 142279, Moscow region, Serpukhov district, p. Obolensk.

Studies on decontamination of airspace were carried out in medical institutions in Moscow and the Moscow region. based on accredited hygiene and epidemiology centers.

The bactericidal properties of gel preparations (Sensitive - No. 1, Tageton - No. 2) were studied on laboratory strains of M. tuberculosis H 37 RV (p). The therapeutic effect was investigated using the infectious model in small laboratory animals (mice): acute tuberculosis infection caused by M. tuberculosis H 37 RV (p) with intravenous administration and five-fold treatment in a day. Aerosol treatment with drugs No. 1; No. 2 was started 7 days after infection in a 1: 1 dilution with distilled water in the nebulizer of the aerosol chamber, (calculated concentration of the preparations was 0.1 μg / L). Euthanasia was performed on day 30 and was accompanied by seeding from the organs (to determine CFU). Sowing was carried out by 10-fold dilution in PBS with 0.05% Tween-80 on a solid 7H11 medium with the addition of 10% cattle serum, 100 μl per cup. The incubation of crops was carried out at a temperature of 37 (+/- 1) ° C for 21 days. The study of the effectiveness of treatment with drugs on the content of bacteria in the organs and the results are shown in table No. 2.

Table number 2 No. p / p name of authority control (PFR) CFU per organ drug number 1 CFU per organ drug №2 CFU per organ one lung spleen 1.3 × 10 ⁷ 1.6 × 10 ⁶ 1.1 × 10 ⁶ 1.1 × 10 ⁶ 4.5 × 10 ⁵ 3.2 × 10 ⁵ 2 lung spleen 1.6 × 10 ⁷ 1.8 × 10 ⁶ 4.3 × 10 ⁶ 1.3 × 10 ⁶ 4.8 × 10 ⁵ 3.6 × 10 ⁵ 3 lung spleen 2.6 × 10 ⁷ 2.1 × 10 ⁶ 2.7 × 10 ⁶ 1.5 × 10 ⁶ 3.7 × 10 ⁵ 2.4 × 10 ⁵ four lung spleen 2.7 × 10 ⁷ 4.2 × 10 ⁶ 3.1 × 10 ⁶ 1.6 × 10 ⁶ 3.9 × 10 ⁵ 3.8 × 10 ⁵ 5 lung spleen 3.0 × 10 ⁷ 2.6 × 10 ⁶ 3.9 × 10 ⁶ 1.6 × 10 ⁶ 3.9 × 10 ⁵ 3.5 × 10 ⁵ 6 lung spleen 2.7 × 10 ⁷ 1.9 × 10 ⁶ 3.0 × 10 ⁶ 1.6 × 10 ⁶ 4.1 × 10 ⁵ 3.8 × 10 ⁵ 7 lung spleen 1.0 × 10 ⁷ 2.5 × 10 ⁶ 2.7 × 10 ⁶ 1.6 × 10 ⁶ 4.4 × 10 ⁵ 3.9 × 10 ⁵ 8 lung spleen 1.6 × 10 ⁷ 1.8 × 10 ⁶ 1.3 × 10 ⁶ 1.1 × 10 ⁶ 3.8 × 10 ⁵ 3.1 × 10 ⁵ 9 lung spleen 2.11 × 10 ⁷ 2.2 × 10 ⁶ 3.4 × 10 ⁶ 1.9 × 10 ⁶ 4.3 × 10 ⁵ 4.0 × 10 ⁵ 10 lung spleen 1.91 × 10 ⁷ 2.3 × 10 ⁶ 2.93 × 10 ⁶ 1.7 × 10 ⁶ 4.5 × 10 ⁵ 4.1 × 10 ⁵ average value lay down. 2.1 × 10 ⁷ 2.8x10 ⁶ 4.2 × 10 ⁵ the average value of the sles 2.3 × 10 ⁶ 1.7x10 ⁶ 3.8 × 10 ⁵

Figure 1 shows the assessment of the therapeutic effect of the use of the compositions.

The results of the evaluation of the therapeutic effect of gel preparations showed that the aerosol-injected preparation No. 2 is more active, both compositions are non-toxic during aerosol delivery to the lungs.

Figure 2 presents a chart of the effectiveness of the proposed composition for air purification in medical facilities.

As a result of the use of a composition from a suspension of liposomes, a reduction in the level of air contamination is achieved by a factor of 2–3 30 minutes after aerosol treatment of the premises by 10 presses on the metering trigger with an area of 20 mV. The maximum effect of reducing the microbial number was noted one day after application.

During the research (more than 30 rooms, including hospital wards), no cases of allergic reactions were recorded. The presence of active molecules in the air in the same concentration has a general strengthening effect on humans and inhibits the growth and development of microorganisms. This is the specificity of the action of natural antiseptics, which often exhibit a pronounced therapeutic effect. This is the mechanism of action of phytoncides, whose molecules are similar in chemical structure and biological effect to endogenous compounds involved in the regulation of physiological reactions of living organisms

Claims (3)

1. Composition of a suspension of liposomes for the prevention and treatment of airborne infections, in particular tuberculosis, characterized in that it contains lipofolk, propylene glycol extract from pine wood, propylene glycol extract of sage, essential oils of marigold, monarda and eucalyptus, carbopol, glycerin, blanose , epophene, cato, sodium hydroxide and water in the following ratio of components, wt.%:
lipofolk 0.1-5.0 pine wood propylene glycol extract 0.1-1.2 sage propylene glycol extract 1.0-2.0 marigold essential oil 0.3-0.9 monarda essential oil 0.1-0.7 eucalyptus essential oil 0.01-0.1 carbopol 0.1-0.5 glycerol 0.5-3.0 blanose 0.01-0.1 epofen 0.001-0.1 caton 0.01-0.1 sodium hydroxide 0.3-0.7 water rest 2. A composition of suspended liposomes for the prevention and treatment of airborne infections, in particular tuberculosis, characterized in that it contains lipofolk, propylene glycol extract from pine wood, propylene glycol extracts of dandelion, burdock and cornflower, essential oils of lavender, bergamot and Chinese magnolia vine, carbopol, glycerin, blanose, epofen, caton, sodium hydroxide and water in the following ratio of components, wt.%:
lipofolk 0.2-5.0 pine wood propylene glycol extract 0.05-1.0 dandelion propylene glycol extract 0.5-1.0 burdock propylene glycol extract 0.3-0.7 cornflower propylene glycol extract 0.7-1.4 lavender essential oil 0.1-0.5 bergamot essential oil 0.1-0.7 Chinese Schisandra essential oil 0.05-0.2 carbopol 0.1-0.5 glycerol 0.5-3.0 blanose 0.01-0.1 epofen 0.001-0.1 caton 0.01-0.1 sodium hydroxide 0.2-0.6 water rest 3. A method for the prevention and treatment of airborne infections, in particular tuberculosis, by an aerogenous route, characterized in that the aerosol treatment of the room is carried out with a composition of suspended liposomes according to claim 1 or 2, by carrying out 10 presses on the dispensing trigger with an area of 20 square meters.

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